Extracellular Vesicles for the Treatment of Syringomyelia

An Exploratory Study on the Use of Intrathecal Injection of Human Autologous Mesenchymal Stromal Cells Derived Extracellular Vesicles for the Treatment of Syringomyelia

This is a open-label, single-arm, dose escalation phase I clinical trial. The goal of this clinical trial is to evaluate the safety and preliminary efficacy of Intrathecal injection human umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicle (hUC-MSC-sEV) in syringomyelia.

Study Overview

• Status: Recruiting
• Conditions: Syringomyelia
• Intervention / Treatment: Drug: Exosomes group

Detailed Description

This is a open-label, single-arm, dose escalation phase I clinical trial. The study will consist of one part: Part 1 will be a dose-escalation study.

A traditional 3+3 dose-escalation design will be implemented in Part 1. Cohort 1 will receive low-dose1×1011particles; Cohort 2 will receive middle-dose2×1011particles; and Cohort 3 will receive high-dose3×1011particles. (Cohort 1 to Cohort 3 will receive a dose of 2 ml per lumbar puncture, administered once a month, for a total of three months.) If no dose-limiting toxicities (DLTs) are observed for 2 weeks after the administration of the first Intrathecal injection, a new cohort will be enrolled at the next planned dose level. If DLTs are observed in one participant in the cohort, an additional three participants will be treated at the same dose level. Dose escalation will be stopped if DLTs are observed in more than 33% of the participants.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: chenghua yuan; Phone Number: +861083198899; Email: yuanchenghua@ccmu.edu.cn
• Study Contact Backup: Name: fengzeng jian, md; Phone Number: +861083198899; Email: jianfengzeng@xwh.ccmu.edu.cn

Study Locations

• China
  • Beijing City
    • Beijing, Beijing City, China, 100032
      • Recruiting
      • Xuanwu Hospital
      • Contact: fengzeng jian; Phone Number: 01083198899; Email: jianfengzeng@xwh.ccmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients whose MR revealed that syrinx have shrunk after surgery for a year but whose clinical spinal cord symptoms have not improved.
• Patients whose MR revealed that syrinx spontaneously resolution under conservative observation, but whose clinical spinal cord symptoms have not improved.
• Age: 18-70 years, inclusion of both genders;

Exclusion Criteria:

• 1. Those with diabetes, heart disease, or impaired liver or kidney function; 2. Those with other diseases such as brainstem tumors and spinal cord tumors; 3. Infected individuals with lumbar puncture sites; 4. Those with previous or detected abnormalities in the heart; 5. Those who have autoimmune diseases and need to be treated with immunosuppressants; 6. Those who are allergic to the research drugs; 7. Have participated in other interventional clinical studies or received other cell therapies (excluding blood transfusion) within the past three months; 8. Those who are unconscious, unable to express subjective discomfort symptoms and unable to cooperate with neurological function tests, those who have been receiving drug treatment for a long time and do not cooperate with the treatment plan; 9. Pregnant women, women who are breastfeeding and those planning to become pregnant; 10. Serological tests (HBsAg, anti-HCV, anti-HIV, TP-Ab) are positive; 11. Other circumstances where the researcher deems the patient unsuitable to participate in this study (including but not limited to not meeting the treatment that benefits the patient the most, poor patient compliance, abnormal laboratory test indicators that cannot be accepted, etc.).

Rejection Criteria:

misdiagnosis; use of any medication that may significantly impact the assessment accuracy of hUC-MSC-sEV engraftment; absence of any evaluation outcome at any time point during the follow-up period

Cessation Criteria:

individual wishes of the subjects; occurrence of any hUC-MSC-sEV-associated serious adverse event (SAE) that may aggravate neurological dysfunction, or require prolongation of existing hospitalization, or need hospital readmission, or impair consciousness, or be life-threatening, or even lead to death in any subject; detection of any major mistake in the present protocol during the implementation of this clinical trial; the national administration agency requires the clinical trial to be halted

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exosomes group; Patients in this arm will receive exosomes derived from human umbilical cord blood mesenchymal stem cells as a Intrathecal injection, administered once a month, for a total of three months.	Drug: Exosomes group; Exosomes derived from human umbilical cord blood mesenchymal stem cells for Intrathecal injection (administered once a month, for a total of three months, based on the recommended dose during the dose-escalation phase).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who experienced dose-limiting Toxicities (DLTs)	DLTs related to hUC-MSC-sEV include adverse events of grade 3 or higher (including significant clinical laboratory findings) that are possibly, likely, or definitely related to the study drug, accompanied by clinical symptoms and requiring medical treatment within 14 days of administration. Adverse events are graded according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).	24 hours, 4±1 Weeks, 8±1 Weeks,12±1 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
American Spinal Injury Association(ASIA) Score	American Spinal Injury Association(ASIA) Score for evaluating the spinal cord function， degree of the spinal cord function, motor1-100, sensory 1-224, higher scores mean a better outcome	4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
Klekamp and Sammi syringomyelia scale	for evaluating the spinal cord function, each score 1-5, higher scores mean a better outcome	4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
Incidence of severe adverse events	The proportion of patients who experienced severe adverse events.	4±1 Weeks, 8±1 Weeks,12±1 Weeks
Time to event (death, tracheostomy, and permanent assisted mechanical ventilation)	The number of time-to-event outcomes.	up to 12 months
modified Japanese Orthopaedic Association Scores (mJOA)	Motor function， sensory， bladder function；for evaluating the spinal cord function；0-17， higher scores mean a better outcome	4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
xuanwu syringomyelia scale	for evaluating the spinal cord function, for evaluating the spinal cord function；0-18， higher scores mean a worse outcome	4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
improvement or resolution of the syrinx	improvement in size.	4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the blood and csf markers.	A number of blood and csf markers will be examined.	4±1 Weeks, 8±1 Weeks,12±1 Weeks
Change from baseline in the neuroimaging indices.	Neuroimaging indices include DTI, DTI-ALPS.	4±1 Weeks, 8±1 Weeks,12±1 Weeks
Change from baseline in the Electrophysiological indices.	Electrophysiological indices include EMG.	4±1 Weeks, 8±1 Weeks,12±1 Weeks
Change from baseline in the neuroimaging indices.	Neuroimaging indices include QSM.	4±1 Weeks, 8±1 Weeks,12±1 Weeks
Change from baseline in the Electrophysiological indices.	Electrophysiological indices include Somatosensory evoked potential .	4±1 Weeks, 8±1 Weeks,12±1 Weeks
Change from baseline in the Electrophysiological indices.	Electrophysiological indices include Motor Evoked Potential.	4±1 Weeks, 8±1 Weeks,12±1 Weeks

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Collaborators: Yisaier Medical Technology (shan xi) Co., Ltd.

Publications and helpful links

General Publications

• Yuan C, Du Y, Yao Q, Zhang C, Zhang L, Liu Z, Wang K, Duan W, Wang Z, Wang X, Zeng G, Wu H, Chen Z, Heiss JD, Guan J, Jian FZ. Natural history of Chiari I malformation-syringomyelia: longitudinal cohort study. J Neurol Neurosurg Psychiatry. 2025 Nov 13;96(12):1204-1214. doi: 10.1136/jnnp-2025-336023.
• Krause M, Gburek-Augustat J, Grafe D, Metzger R, Ginzel M, Griessenauer CJ, Grassner L, Weghuber D, Gradl J, Auer D, Schally T, Rund S, Kals C, Folie C, Bayer E, Gimona M, Rohde E. First-In-Human Application of Human Umbilical Cord-Derived Extracellular Vesicles in Tethered Spinal Cord Release Surgery. J Extracell Vesicles. 2025 Jun;14(6):e70104. doi: 10.1002/jev2.70104.
• Vaquero J, Zurita M, Rico MA, Aguayo C, Fernandez C, Rodriguez-Boto G, Marin E, Tapiador N, Sevilla M, Carballido J, Vazquez D, Garcia-Olmo D, Guadalajara H, Leon M, Valverde I; Neurological Cell Therapy Group From Puerta De Hierro-Majadahonda Hospital. Cell therapy with autologous mesenchymal stromal cells in post-traumatic syringomyelia. Cytotherapy. 2018 Jun;20(6):796-805. doi: 10.1016/j.jcyt.2018.04.006. Epub 2018 May 18.
• Li M, Wang X, Qi B, Cui S, Zheng T, Guan Y, Ma L, Liu S, Li Q, Chen Z, Jian F. Treatment of Syringomyelia Characterized by Focal Dilatation of the Central Canal Using Mesenchymal Stem Cells and Neural Stem Cells. Tissue Eng Regen Med. 2024 Jun;21(4):625-639. doi: 10.1007/s13770-024-00637-1. Epub 2024 Apr 5.

Study record dates

Study Major Dates

• Study Start (Actual): December 23, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 19, 2025

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: spinal cord injury; mesenchymal stromal cell; syringomyelia; extracellular vesicle
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries; Syringomyelia
• Other Study ID Numbers: XWhUC-MSCs-EV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study will not share individual participant data to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No